: The objective of the proposed research is to define cis-acting elements and transcription factors that mediate CYP19 expression in the appropriate tissue-/cell-specific and developmentally regulated manners. Transgenic mice will be created carrying chimeric reporter gene constructs comprised of DNA flanking placenta-specific exon I.1, ovary/testis-specific exon II, and adipose/fetal liver-specific expression. The molecular basis for 'promoter switching' will be analyzed in transgenic mice bearing endocrine-responsive mammary and liver tumors. Transfected human trophoblasts in primary culture will be used to define the cis-acting elements that are required for syncytiotrophoblast-specific CYP19 promoter I.1 expression. Once gene regulatory elements are defined, they will be used to isolate cDNAs encoding transcription factors that mediate syncytiotrophoblast-specific CYP19 gene expression. It is proposed to continue to characterize transcription factors that mediate syncytiotrophoblast differentiation and its regulation by hypoxia/O2 and to define their expression in preeclampsia.